Hepatocyte expression of TRAIL pathway regulators correlates with histopathological and clinical parameters in chronic HCV infection.

BACKGROUND AND AIMS: Treatment with pegylated interferon-alpha (PEG-IFN) and ribavirin is the backbone of standard therapy of HCV by mechanisms that are not completely understood. Besides a direct antiviral effect, different immunomodulatory and apoptotic effects have been discussed. Tumor necrosis factor-related apoptosis inducing-ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family with immunomodulatory as well as pro- and antiapoptotic effects and is putatively involved in control of HCV infection. Thus, we analyzed the expression of the TRAIL/TRAIL-receptor system, caspase-8 and cFLIP and examined their prognostic and predictive value for HCV infection and antiviral therapy, respectively. METHODS: We immunohistochemically analyzed liver biopsies of 116 therapy-naive HCV patients before treatment with PEG-IFNα and ribavirin in comparison to healthy liver tissue. Expression levels of TRAIL, TRAIL-R1 to TRAIL-R4, caspase-8 and cFLIP were correlated with sustained virologic response (SVR), genotype and staging of chronic hepatitis. RESULTS: Caspase-8, cFLIP, TRAIL-R2 and TRAIL-R4 were strongly upregulated in HCV patients, whereas TRAIL-R3 was downregulated. SVR correlated with high expression of TRAIL and pro-apoptotic TRAIL-R2 on HCV infected hepatocytes. CONCLUSIONS: Our results suggest a pathophysiological role of TRAIL in both, HCV infection and therapy. Further studies need to elaborate possible TRAIL-related targets for clinical applications.

The effects of individualized therapeutic programs on chronic hepatitis C and the influential factors of virological response / 中华内科杂志

Objective To investigate the effect of individualized therapeutic programs with combination of interferon and ribavirin (RBV) in chronic hepatitis C (CHC) and study the influential factors of virological response rates.Methods A total of 139 patients with CHC were enrolled and given the intensive treatment doses of interferon and RBV according to their basic clinical condition.At the treatment of 0,4,12,24 weeks,the end of treatment and 24 weeks after treatment stop,the serum HCV RNA was determined.Timely adjustment to dosage and time periods was made according to the virological response to treatment,and the predictive value of rapid virological response (RVR) and complete early virological response (cEVR) for sustained virological response (SVR) were analyzed.Results At the 4th week of treatment,the level of serum HCV RNA was monitored in 120 patients,and 84.2％ (101/120) of patients obtained RVR; among them,90.7％ (88/97) obtained SVR.The virus load of patients obtained RVR at pretherapy was lower than that of patients didn't obtained RVR [(5.883±1.246) lg copies/ml vs (6.502±0.693)lg copies/ml,P =0.034].The RVR rate of initial treatment patients with PEG-IFNα-2a [87.8％(79/90)]was significantly higher than that of retreatment patients with PEG-IFNα-2a [65.0％ (13/20)](P =0.031).At the 12th week of treatment,the level of serum HCV RNA was monitored in 132 patients,and 92.4％ (122/132) of patients obtained cEVR; among them,90.8％ (108/119) obtained SVR.The SVR rate of patients obtained cEVR was significantly higher than that of patients didn't obtained cEVR (5/9) (P =0.007).There was no significant difference between the cEVR rate of initial treatment patients [94.7％ (90/95)]and retreatment patients [85％ (17/20)]with PEG-IFNα-2a (P =0.158).Conclusions cEVR was predictor of SVR.Individualized therapy can increase the obtaining probability of RVR,cEVR and SVR.Adjusting drug dose timely and extending treatment period of HCV RNA-negative based on virological response to treatment are important in CHC individualized therapy.